Document Detail

Heterodimerization with different Jun proteins controls c-Fos intranuclear dynamics and distribution.
MedLine Citation:
PMID:  20053986     Owner:  NLM     Status:  MEDLINE    
The c-Fos proto-oncogenic transcription factor defines a multigene family controlling many processes both at the cell and the whole organism level. To bind to its target AP-1/12-O-tetradecanoylphorbol-13-acetate-responsive element or cAMP-responsive element DNA sequences in gene promoters and exert its transcriptional part, c-Fos must heterodimerize with other bZip proteins, its best studied partners being the Jun proteins (c-Jun, JunB, and JunD). c-Fos expression is regulated at many transcriptional and post-transcriptional levels, yet little is known on how its localization is dynamically regulated in the cell. Here we have investigated its intranuclear mobility using fluorescence recovery after photobleaching, genetic, and biochemical approaches. Whereas monomeric c-Fos is highly mobile and distributed evenly with nucleolar exclusion in the nucleus, heterodimerization with c-Jun entails intranuclear redistribution and dramatic reduction in mobility of c-Fos caused by predominant association with the nuclear matrix independently of any binding to AP-1/12-O-tetradecanoylphorbol-13-acetate-responsive element or cAMP-responsive element sequences. In contrast to c-Jun, dimerization with JunB does not detectably affect c-Fos mobility. However, dimerization with JunB affects intranuclear distribution with significant differences in the localization of c-Fos.c-Jun and c-Fos.JunB dimers. Moreover, c-Jun and JunB exert comparable effects on another Fos family member, Fra-1. Thus, we report a novel regulation, i.e. differentially regulated intranuclear mobility and distribution of Fos proteins by their Jun partners, and suggest the existence of intranuclear storage sites for latent c-Fos.c-Jun AP-1 complexes. This may affect the numerous physiopathological functions these transcription factors control.
Cécile E Malnou; Frédérique Brockly; Cyril Favard; Gabriel Moquet-Torcy; Marc Piechaczyk; Isabelle Jariel-Encontre
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-01-06
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  285     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-02-22     Completed Date:  2010-03-26     Revised Date:  2011-07-25    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6552-62     Citation Subset:  IM    
Institut de Génétique Moléculaire de Montpellier, UMR5535, CNRS, 1919 route de Mende, 34293 Montpellier Cedex 5, France.
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MeSH Terms
Cell Line
Cell Nucleus / chemistry,  metabolism
Hela Cells
Multiprotein Complexes / metabolism
Protein Multimerization
Protein Transport
Proto-Oncogene Proteins c-fos / metabolism*
Proto-Oncogene Proteins c-jun / metabolism*
Transcription Factor AP-1 / metabolism*
Transcription Factors / metabolism
Reg. No./Substance:
0/Multiprotein Complexes; 0/Proto-Oncogene Proteins c-fos; 0/Proto-Oncogene Proteins c-jun; 0/Transcription Factor AP-1; 0/Transcription Factors; 0/fos-related antigen 1

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